Aggregation or agglutination of molecules or cells forms the basis of various useful biological assays. Hemagglutination, or haemagglutination, is a specific form of agglutination that involves red blood cells (RBCs). This phenomenon is used in the laboratory to determine blood type, the presence and/or quantity of virus in a blood sample, and/or the quantity of certain anti-infectious agent antibodies. Hemagglutination causes RBCs to form macroscopic lattice structures that are stable against moderate agitation. These structures can be distinguished from non-agglutinated RBCs by visual observation, which forms the basis of a variety of traditional assay methods.
Hemagglutination can be triggered by viruses, bacteria, antibodies, and other factors (e.g. lectins). For example, antibodies that bind to type A antigens will induce hemagglutination in samples containing type A or AB RBCs. Similarly, viruses and viral antigens that bind to cell surface molecules can induce hemagglutination. Viruses may contain the protein “hemagglutinin”, which binds to molecules on host cells. For example, hemagglutinin proteins may bind to sialic acid on the membrane of host cells such as RBCs. Viral titer can be approximated by observing hemagglutination at various dilutions of a sample containing virus. Bacteria can also be detected and quantified with these methods.
Despite the highly useful applications of hemagglutination assays, current methods are relatively slow, subjective, and unreliable for some purposes. Traditional pre-treatment protocols can take as long as 12-24 hours, and visual inspection is not a robust method for making quantitative determinations. Hemagglutination assays are often conducted in settings where time is of the essence (e.g. to prevent spread of a viral outbreak or during an emergency blood transfusion). Therefore, there is a considerable need in the art for improved methods of detecting and measuring aggregation/agglutination.